Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Barriers to Veterans Health Administration Care in a Nationally Representative Sample of Women Veterans

BACKGROUND: Women veterans are generally less healthy than their nonveteran female counterparts or male veterans. Accumulating evidence suggests there may be barriers to women veterans' access to and use of Veterans Health Administration (VHA) care. OBJECTIVE: To document perceived and/or actual barriers to care in a nationally representative sample of women veterans and examine associations with VHA use. DESIGN: Cross-sectional telephone survey. PARTICIPANTS: Women who are current and former users of VHA from VA's National Registry of Women Veterans. MEASUREMENTS: Assessments of perceptions of VHA care, background characteristics, and health service use. RESULTS: Perceptions of VHA care were most positive regarding facility/physical environment characteristics and physician skill and sensitivity and least positive regarding the availability of needed services and logistics of receiving VHA care (M=0.05 and M=−0.10; M=−0.23 and M=−0.25, respectively). The most salient barrier to the use of VHA care was problems related to ease of use. Moreover, each of the barriers constructs contributed unique variance in VHA health care use above and beyond background characteristics known to differentiate current users from former VHA users (Odds ratio [OR]=4.03 for availability of services; OR=2.63 for physician sensitivity and skill: OR=2.70 for logistics of care; OR=2.30 for facility/physical environment). Few differences in barriers to care and their association with VHA health care use emerged for women with and without service-connected disabilities. CONCLUSIONS: Findings highlight several domains in which VHA decisionmakers can intervene to enhance the care available to women veterans and point to a number of areas for further investigation